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Preparation, <i>In-vitro, Ex-vivo</i>, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based <i>In Situ</i> Gel
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Background:

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.

Objective:

This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.

Method:

Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.

Result:

The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.

Conclusion:

NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

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Publication Date
Sat Oct 29 2022
Journal Name
Current Trends In Geotechnical Engineering And Construction (pp.52-61)
Drinking Water Assessment Using Statistical Analyses of AL-Muthana Water Treatment Plant
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Publication Date
Sun Jun 30 2024
Journal Name
Science And Technology Indonesia
Evaluating the Biocompatibility of Maxillofacial Silicone Enhanced by Hexagonal Boron Nitride Particles
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This study aims to evaluate the biocompatibility of a novel filler material intended to improve the longevity of polymer systems used in prosthetics in respect of cytotoxicity and skin irritation. RTV50F silicone elastomer incorporated with various percentages of hexagonal boron nitride (H-BN) (0.1, 0.3, 0.5, 0.7, and 1 wt%) have been tested. Silicone without H-BN was utilized as the control for comparison. The in vitro cytotoxicity test includes specimens (n=18) with 10 mm in diameter and 2 mm in thickness applied directly to the normal human fibroblast cell line (NHF) and incubated for 72 hours, then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell viability. The skin irritati

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Publication Date
Mon Jun 01 2015
Journal Name
Journal Of Engineering
Using Nanoparticles for Enhance Thermal Conductivity of Latent Heat Thermal Energy Storage
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Phase change materials (PCMs) such as paraffin wax can be used to store or release large amount of energy at certain temperature at which their solid-liquid phase changes occurs. Paraffin wax that used in latent heat thermal energy storage (LHTES) has low thermal conductivity. In this study, the thermal conductivity of paraffin wax has been enhanced by adding different mass concentration (1wt.%, 3wt.%, 5wt.%) of (TiO2) nano-particles with about (10nm) diameter. It is found that the phase change temperature varies with adding (TiO2) nanoparticles in to the paraffin wax. The thermal conductivity of the composites is found to decrease with increasing temperature. The increase in thermal conductivity ha

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Publication Date
Sat Dec 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
Finding the best estimation of generalized for failure rates by using Simulation
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The statistical distributions study aimed to obtain on best descriptions  of variable sets phenomena, which each of them got one behavior of that distributions .  The estimation operations study for that distributions considered of important things which could n't canceled in variable behavior study, as result  this research came as trial for reaching to best method for information distribution estimation which is generalized linear failure rate distribution, throughout studying the theoretical sides by depending on statistical posteriori methods  like greatest ability, minimum squares method and Mixing method (suggested method).        

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Publication Date
Wed Nov 14 2018
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Simulation of Batch Reactive Distillation for Biodiesel Production from Oleic Acid Esterification
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The present work concerns with simulating unsteady state equilibrium model for production of methyl oleate (biodiesel) from reaction of oleic acid with methanol using sulfuric acid as a catalyst in batch reactive distillation. MESHR equations of equilibrium model were solved using MATLAB (R2010a). The validity of simulation model was tested by comparing the simulation results with a data available in literature. UNIQUAC liquid phase activity coefficient model is the most appropriate model to describe the non-ideality of OLAC-MEOH-MEOL-H2O system. The chemical reactions rates results from EQ model indicating the rates are controlled by chemical kinetics. Several variables was studied such as molar ratio of methanol to oleic acid 4:1, 6:1

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Publication Date
Tue Nov 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Use Dynamic Bayesian network to estimate the reliability of Adamia Water Network
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Abstract\

In this research, estimated the reliability of water system network in Baghdad was done. to assess its performance during a specific period. a fault tree through static and dynamic gates was belt and these gates represent logical relationships between the main events in the network and analyzed using dynamic Bayesian networks . As it has been applied Dynamic Bayesian networks estimate reliability by translating dynamic fault tree to Dynamic Bayesian networks and reliability of the system appreciated. As was the potential for the expense of each phase of the network for each gate . Because there are two parts to the Dynamic Bayesian networks and two part of gate (AND), which includes the three basic units of the

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Publication Date
Sun Mar 01 2020
Journal Name
Iraqi Journal Of Physics
Increasing the conversion efficiency of KTP crystal using the pump-power technique
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In this study, the effect of pumping power on the conversion efficiency of nonlinear crystal (KTP) was investigated using laser pump-power technique. The results showed that the higher the pumping power values, the greater the conversion efficiency (η) and, as the crystal thickness increases within limitations, the energy conversion efficiency increases at delay time of (0.333 ns) and at room temperature. Efficiency of 80% at length of KTP crystal (L = 1.75 X 10-3 m) and Pin = 28MW, and also, compare the experimental results with numerical results by using MATLAB program. 

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Publication Date
Mon Mar 08 2021
Journal Name
Surgical Neurology International
Ruptured giant aneurysm of a cortical middle cerebral artery: A case report
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Background:

Aneurysms of the cortical branches of the middle cerebral artery (MCA) are rare. They usually are secondary to traumatic or infectious etiologies and are rarely idiopathic. The specific characteristics of idiopathic aneurysms in such location are not well defined in the literature. The authors report a rare case of a ruptured giant idiopathic cortical MCA aneurysm with review of the available literature on this clinical entity.

Case Description:

A 24-year-old female presented with headache, disturbed level of consciousness, and right-sided weakness. Imaging studies showed a left frontoparietal intracer

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Publication Date
Tue Sep 11 2018
Journal Name
Iraqi Journal Of Physics
Manufacturing of porous refractories from Iraqi Kaolin by adding expanded polystyrene waste
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Fabrication of porous clay refractory insulating specimens from Iraqi kaolin with different percentage of Expanded Polystyrene (EPS) waste crumbs additions were investigated. After mixing and forming by hand molding, the specimens was dried and fired at 1300 oC. The structural, physical, mechanical and thermal properties of the refractory insulating products were measured. Maximum addition of EPS (1.25 wt%) lead to reduce the linear shrinkage to less than 1.7% and increased apparent porosity up to 50 %. As well as, the density, Modulus of rupture and thermal conductivity were reduced to 1.39 g/cm3, 4.1 MPa and 0.21 W/m.K, respectively. The final outcome, addition of EPS showed good results in the formation of pores without distorting the

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Publication Date
Tue Oct 30 2018
Journal Name
Https://www.researchgate.net/journal/civil-engineering-journal-2476-3055
Developing Water Quality Index to Assess the Quality of the Drinking Water
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In the present study, an attempt has been to develop a new water quality index (WQI) method that depends on the Iraqi specifications for drinking water (IQS 417, 2009)  to assess the validity of the Euphrates River for drinking by classifying the quality of the river water at different stations along its entire reach inside the Iraqi lands. The proposed classifications by this method are: Excellent, Good, Acceptable, Poor, and Very poor. Eight water quality parameters have been selected to represent the quality of the river water these are: Ion Hydrogen Concentration (pH), Calcium (Ca), Magnesium (Mg), Sodium (Na), Chloride (Cl), Sulphate (SO_4), Nitrate (NO_3), and Total Dissolved Solids (TDS). The variation of the water quality p

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